The trapeziometacarpal (TMC) joint is the most common site of disabling osteoarthritis (OA) in the upper limb and has a strong predilection for postmenopausal women. The ratio of women to men for basal joint reconstructive procedures for OA is 10-20:1. Structurally, the TMC joint is a complex biconcave saddle- shaped joint with limited bony constraint. While muscles provide the active dynamic stabilization of the joint, surrounding ligaments are the major static stabilizers of the joint. Previous pathologic studies suggest a potential etiologic relationship between the beak ligament (primary TMC stabilizing ligament) degeneration and the TMC OA. Despite extensive pathophysiologic studies in TMC joint, the TMC OA mechanism with 10-20 fold increase in postmenopausal women remains unclear. Estrogen, the primary female sex hormone that significantly diminishes after menopause, has been found to interfere with the soft tissue homeostasis. We hypothesize that primary attritional changes in the beak ligament insertions mediated by estrogen receptors (ER a&b), affect the structural integrity and kinematic function of the beak ligament. Joint instability secondary to the beak ligament attrition is suspected to further change the local TMC mechanical environment which may initiate/accelerate the TMC OA progression in postmenopausal females. To validate the hypothesis, we aim to: 1) in vitro study: determine the localized morphological, mechanoelectrical, and biochemical changes of the beak ligament in relation to estrogen receptor expression and tissue bound estradiol levels; 2) in vitro study: develop a musculoskeletal function assessment system to determine the impact of beak ligament laxity/detachment on TMC kinematics and local joint environment; 3) in vivo validation: validate the morphometric patterns and kinematic function of the beak ligament in a cohort of female human subjects at various OA stages. Successful completion of this proposal will fill the knowledge gap with robust data regarding negative impact of estrogen deficiency on beak ligament integrity and kinematic function in postmenopausal females. It will support further understanding the biological and mechanical factors interaction on beak ligament integrity and function in our future larger scale study. This project intends to shift the current TMC pathomechanics research paradigm from articulating surface to surrounding beak ligament toward our long-term goals regarding early diagnosis and management of OA - a complementary ligament morphometric grading and a TMC kinematic classification system will be introduced for OA diagnosis in addition to the commonly used Eaton-Littler classification system; it will lead to a local TMC OA management strategy focusing on beak ligament insertion preservation. Integrating both experimental and numeri IMH focus of patient-specific modeling for virtual human trials.